Chapter 3 │ Page 94 processes and signaling pathways a ected, which could ultimately help us predict potential downstream immunological e ects. Examining the row clustering, including the di erent cell lines, therapies and time points, we could appreciate a pattern that aligned with our earlier observations in expression data. Specifically, the Cal27 and SCC61 cell line tended to form distinct clusters separate from SCC22B cells, and the spheroids from the CDDP monotherapies and combination treatments also grouped together, respectively. Clustering of cytokines and chemokines was visualized through dendrograms in the column analysis, revealing two distinct clusters. The first cluster included IL-8, IL-10, IL-1β, and the chemokine CCL4, which exhibited an upregulation trend in response to CDDP monotherapy. In contrast, the second cluster comprised CCL5, CXCL10, and IFN-β, which were predominantly downregulated following NTP exposure, both as a monotherapy and in combination treatments. This clustering suggests distinct immunomodulatory e ects of CDDP and NTP, leading to di erential regulation of cytokine and chemokine expression depending on the treatment modality. While these clustering patterns provide valuable insights into treatmentdependent cytokine and chemokine signaling, their intrinsic dual roles in both pro- and anti-tumor immunity make it hard to fully interpret the global, functional impact in an in vitro setting. A deep understanding of NTP-CDDP immune regulation requires assessment in a complete biological system, where also the interplay between di erent immune components is taken into account in a relevant tumor microenvironment context. Therefore, the next step was to investigate the immunogenicity of NTP-CDDP therapy in an in vivo HNSCC model. 3.5 NTP-Based Vaccination Enhances Survival and Reduced Tumor Kinetics and Risk in vivo The in vitro evaluation of the immunogenicity of our novel NTP-CDDP combination therapy was focused on the detection of several key DAMPS, cytokines and chemokines that play crucial roles in ICD by shaping the immune response and
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